PURPOSE: Passive leg raising (PLR) is a maneuver performed to test the cardiac Frank-Starling mechanism. We assessed the influence of PLR-induced changes in preload on the performance of PLR-induced change in pulse pressure (Delta(PLR)PP) and cardiac output (Delta(PLR)CO) for fluid responsiveness prediction. METHODS: Sedated, nonarrhythmic patients with persistent shock were included in this prospective multicenter study. Cardiac output and pulse pressure were measured at baseline (patient supine), during PLR (lower limbs lifted to 45 degrees) and after 500-ml volume expansion. Patients were classified as responders or not. RESULTS: In the whole population (n = 102), the area under the receiver-operating characteristic curve (AUC) was 0.76 for Delta(PLR)PP and was higher for Delta(PLR)CO (0.89)(p < 0.05), but likelihood ratios were close to 1. In patients with a PLR-induced increase in central venous pressure (CVP) of at least 2 mmHg (n = 49), Delta(PLR)PP and Delta(PLR)CO disclosed higher AUCs than in the rest of the population (0.91 vs. 0.66 and 0.98 vs. 0.83; p < 0.05); positive/negative likelihood ratios were 9.3/0.14 (8% cutoff level) and 30/0.07 (7% cutoff level), respectively. CONCLUSIONS: A PLR-induced change in CVP > or =2 mmHg was required to allow clinical usefulness of PLR-derived indices. In this situation, Delta(PLR)PP performed well for predicting fluid responsiveness in deeply sedated patients.